Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)

NCT03018288 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17003417-C-0034
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioblastoma (GBM) refers to a specific kind of brain cancer called glioblastoma. The standard treatment for GBM is radiation plus temozolomide, an oral chemotherapy drug. Pembrolizumab is an immune therapy that is now used to treat other cancers. The addition of pembrolizumab to the standard treatment of radiation and temozolomide has been shown to be well tolerated. Researchers want to see if adding a vaccine made from the person's own tumor will improve the effect of the pembrolizumab. The vaccine which is developed from fresh tumor taken at the time of surgery is called heat shock protein peptide complex-96 (HSPPC-96). Objectives: To see if the adding of pembrolizumab and HSPPC-96 improves the standard treatment for glioblastoma. Eligibility: Adults at least 18 years old with glioblastoma. Design: Participants will be screened with typical cancer tests: Brain scan Medical history Blood and urine tests Questions about quality of life and symptoms These tests will be repeated throughout the study. Participants will have surgery to remove their tumor. A tissue sample from the tumor will be sent to a lab. A vaccine will be made from it. Some participants will get pembrolizumab and vaccine. Some will get pembrolizumab and placebo. Participants will not know which they get. Participants will get radiation for 6 weeks. Participants will take temozolomide by mouth before each treatment. Participants will get pembrolizumab by intravenous (IV) for 30 minutes 3 times over the radiation cycle. Participants will keep taking the 2 drugs every few weeks for about a year. Some may take pembrolizumab for an additional year. Most participants will get the vaccine or placebo after radiation. They will get it 5 times over 6 weeks. Some participants will continue to get the vaccine every few weeks for 1 or 2 years. Participants will repeat the screening tests when they stop study treatment. They will also have follow-up phone calls.

Conditions

Glioblastoma

Keywords

Malignant Gliomas; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• One-year Overall Survival (OS) Rate

  One-year overall survival (OS) rate is defined as the percentage of participants who from time of registration survived to one year in newly diagnosed O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) unmethylated Glioblastoma (GBM) participants treated with radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab followed by Pembrolizumab + TMZ +/- heat-shock protein peptide complex-96 (HSPPC-96) x 6 cycles (1 cycle is 9 weeks) months. Rate of OS is measured by Kaplan-Meier method.

  One year

Secondary Outcomes (10)

• Response Rate

  After treatment, up to 26 months

• Overall Survival (OS)

  Time from registration to the time of death or off study up to 26 months

• Overall Survival at 6, 12 and 24 Months, Post-registration

  6, 12 and 24 months, post-registration

• Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab

  Start of treatment until participant is off study, approximately 61.5 months

• Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab

  Start of treatment until participant is off study, approximately 61.5 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 61.5 months.

Study Arms (4)

1/Temozolomide + Pembrolizumab + Radiation Therapy

OTHER

Standard treatment with experimental treatment (pembro) added.

Drug: Pembrolizumab; Drug: Temozolomide; Procedure: Surgery

2/Temozolomide+Pembrolizumab

EXPERIMENTAL

Temozolomide+Pembrolizumab

Drug: Pembrolizumab; Drug: Temozolomide; Procedure: Surgery

3/Temozolomide+Pembrolizumab+ Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine

EXPERIMENTAL

Temozolomide+Pembrolizumab+ HSPPC96 Vaccine

Drug: Pembrolizumab; Biological: HSPPC-96; Drug: Temozolomide

4/Temozolomide+Pembrolizumab+ Placebo

PLACEBO COMPARATOR

Temozolomide+Pembrolizumab+ Placebo

Drug: Pembrolizumab; Drug: Temozolomide; Other: Placebo

Interventions

Pembrolizumab DRUG

Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy (RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with heat shock protein peptide complex -96 (HSPPC 96) or placebo vaccine if any is available.

Also known as: Keytruda

1/Temozolomide + Pembrolizumab + Radiation Therapy; 2/Temozolomide+Pembrolizumab; 3/Temozolomide+Pembrolizumab+ Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine; 4/Temozolomide+Pembrolizumab+ Placebo

HSPPC-96 BIOLOGICAL

One week post RT, patients will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.

Also known as: heat shock protein peptide complex -96 (HSPPC 96)

3/Temozolomide+Pembrolizumab+ Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine

Temozolomide DRUG

Temozolomide (TMZ) will be administered on day 1 of radiation therapy (before radiation therapy (RT) treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.

Also known as: Temodar

1/Temozolomide + Pembrolizumab + Radiation Therapy; 2/Temozolomide+Pembrolizumab; 3/Temozolomide+Pembrolizumab+ Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine; 4/Temozolomide+Pembrolizumab+ Placebo

Placebo OTHER

One week post radiation therapy (RT), participants will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of Temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.

4/Temozolomide+Pembrolizumab+ Placebo

Surgery PROCEDURE

Tissue for vaccine production and neo-epitope monitoring.

1/Temozolomide + Pembrolizumab + Radiation Therapy; 2/Temozolomide+Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Magnetic resonance imaging (MRI) findings consistent with a suspected glioblastoma (GBM) or a histologically confirmed newly diagnosed GBM that has not been treated and would benefit from further surgical resection. As vaccine needs to be generated from the patient's tumor, patients will need to be identified prior to definitive surgery.
• Preliminary assessment by the neurosurgeons that \>80% of the tumor can be resected with an expectation that \>7gm of tissue would be resected
• Age greater than or equal to 18 years on day of signing informed consent.
• Karnofsky performance status greater than or equal to 70.
• Tumor must be supratentorial only.
• Stereotactic biopsy will not be allowed unless there is plans for second surgery to remove greater than or equal to 80 % of the tumor.
• No prior treatment with radiation or chemotherapy for their GBM.
• No prior treatment with carmustine (Gliadel) wafers.
• Pathology must be a GBM, O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter region determined to be unmethylated and isocitrate Dehydrogenase (IDH) wild type greater than or equal to 80 % resection of contrast enhanced tumor on post operative MRI and greater than 7 grams of tumor resected are required otherwise patient is ineligible.
• Treatment must be initiated greater than or equal to 14 days and \< 6 weeks from surgery.
• Craniotomy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of radiation. Radiation must start within 6 weeks of surgery.
• Dexamethasone dose should be less than or equal to 4 mg/day or steroid equivalent prior to starting treatment. If higher doses are needed, consult with Study Chair.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required.
• Patients must have adequate organ and bone marrow function within 14 days prior to step 2 registration, as defined below:
• Absolute neutrophil count (ANC) \> 1.5 x10(9)/L; platelet count \> 100 x 10(9)/L; and hemoglobin (Hb) \>9.0 g/dL within 7 days prior to step 2 registration. Note: The use of transfusion or other intervention to achieve Hb greater than or equal to 9.0 g/dL is acceptable.

You may not qualify if:

• Known history of immunodeficiency (HIV). This medical entity can be exacerbated by programmed cell death protein 1 (PD-1) blockade.
• History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients who have undergone a bone marrow or stem-cell transplant for any malignancy are excluded.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires chronic systemic steroids or immunosuppressive agents except as noted above. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgren's syndrome will not be excluded from the study.
• Has a history of interstitial lung disease, non-infectious pneumonitis, or pneumonitis.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Examples include:
• Hypertension (defined as 160/95) that is not controlled on medication
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations or substance abuse disorders that would limit compliance with study requirements
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• The effects of pembrolizumab and HSPPC-96 on the developing human fetus are unknown. For this reason and because checkpoint inhibitors and immunotherapeutic vaccines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Has received prior therapy with an anti-PD-1, anti-programmed death-ligand 1 (PD-L1), anti-PD-L2, anti-4-1BB (CD137), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

pembrolizumab; vitespin; Temozolomide; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kevin Camphausen
• Organization: National Cancer Institute

camphauk@mail.nih.gov

240-760-6205

Study Officials

• Kevin Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 12, 2017
• Study Start: September 21, 2017
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: August 8, 2025
• Results First Posted: February 28, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active. All collected individual participant data (IPD) will be available after primary analysis has been published.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)